BioChemical matters

I lecture Biochemistry at a small University in Oporto. Although originally raised as an experimental Biochemist, I have since changed my research into theoretical and computational chemistry and biochemistry. In this blog, I will mostly commment on recent (or not so recent...) research papers that happen to have called my attention. I hope someone will find it interesting/useful :-)

Friday, July 7, 2017

I am now writing a referee report. I usually frame my comments diplomatically and try to be constructive (you will have to take my word for it...). Unfortunately, my first comment to these authors is uncharacteristically harsh, and I wish I had not needed to write it:
"I do understand that productivity and impact metrics like the number of citations, h-index, etc. are wrongly used by intitutions and funding agencies to measure research productivity, and that scientists are implicitly (or explicitly) pressured to inflate them. I cannot, in good conscience, agree with that practice but would have kept silent if a manuscript cited a couple of papers by the authors in the introduction. However, in this manuscript 46 references are cited, of which 23 (number 8-11, 15-19 , 21-23 , 34-42 , 44-45) are from the current authors. None of these 23 citations refers to specific results from those papers: they are rather cited as examples of well-known facts which either require no citation or should cite seminal papers/reviews in the area. I will not accept this paper in any form, for publication in this or any other journal, if those references remain."

I am afraid such comments to authors and editords must become much more common to stop the continuous gaming of the system. As long as metrics are used for ends they were not designed to, authors will (more or less grudgingly) try to game them, if only to ensure that they do not "fall behind" in comparisons with colleagues who feel even less compunction to game. Race to the bottom, and all that...

Thursday, April 28, 2016

Biographies fulfill several different roles: they may simply satisfy one's curiosity over the lives/achievements of the biographees, provide tasty morsels of gossip or interesting stories, or play an "educational" role. Traditionally, the "educational role" of biographies has focused on their presentation of "role models" - whether moral, political or social - or the conditions/life experiences which led to the special significance of the biographee. Scientific biographies follow the same pattern. Like traditional biographies, they are usually limited to people of special significance: trailblazers, mavericks, geniuses, and people who left a mark on their scientific discipline or on the public perception of the worth of their subject.

I wish there were also another kind of biography, devoted to the intelectual careers of "normal" researchers: people who simply follow their intelectual curiosity, who are constrained by the amount of funding they can get and who pass away in obscurity after adding their small contributions to our colective knowledge. I do not want "human interest stories" played by researchers: I rather long for a description of their intelectual journeys, why they decided to study a specific problem, what kinds of mental connections they made (and why), in what measure their interpretation of their results was "commonplace" or (in contrast) specifically triggered by insights coming from seemingly unrelated work they had performed earlier, etc.

I want to read stories that show how each of these normal people, in their own way, made work which seems ordinary but is, in contrast, highly personal: work that would not have been done, or which would not have yielded the same insights, if that scientific question had been tackled by someone with a different research history. I am reasonably confident that most rank-and-file scientists would be fitting subjects for this style of biography, and that the study of these stories would teach us a lot about the roles that creativity, personality, luck and culture play in the fostering of a thriving research environment.

Friday, April 22, 2016

It is said that "No battle plan ever survives contact with the enemy". In my case, the enemy is myself: a permanent inclination towards procrastination, often disguised as an urge to delve deeper into tangentially relevant (or even irrelevant) literature, or to run a new series of computations in yet another interesting system.

And so it came to pass that my plans to increase my manuscript production predictably advanced much more slowly than I had envisioned. In my defence, I can only say that the writing process showed that a few of my computations were not as complete as I expected: a few single-points had converged into an excited state, a couple of transition states had to be newly optimized, etc. But I finally managed to get one manuscript almost ready.

Overall progress on my planned manuscripts:

the reactivity of P450 compound I towards 1,2-dihydroazaborines: Available as a preprint here

computational development of inhibitors of anthrax protective antigen cleavage by furin. No progress

the influence of solute-solvent dispersion/repulsion interactions on the behavior of molecular torsion balances. Analysis of the results does not show any consistent improvement of the fit of computation with experiment upon inclusion of dispersion/repulsion interactions between implicit solvent and solutes

the binding of rubromycin derivatives to telomerase and DNA polymerase. Found serious shortcomings in my AutoDock computations. I have now repeated everything with AutoDock Vina, including flexibility of aminoacid sidechains. 100 ns MD now finishing for three ligands in three candidate binding poses.

the reaction mechanism of copper-catalyzed addition of azides to iodoalkynes. No progress

the reaction mechanism of copper-catalyzed aldol synthesis described by Marek No progress

analysis of molecular determinants of inhibitor binding to monoamine oxidases A and B No progress

Friday, January 1, 2016

Last year, Jan Jensen published his publication plans for 2015. I will do the same this year, mostly as a way to force myself to stop procrastinating, as I have a large backlog of research which is ready for publication (except fo the pesky little detail that I have not started to write the papers).
So here it goes.... This year, I plan to submit my research on :

the reactivity of P450 compound I towards 1,2-dihydroazaborines

computational develoment of lead compunds for inhibition of plasmid-borne DHFR

computational development of inhibitors of anthrax protective antigen cleavage by furin

the influence of solute-solvent dispersion/repulsion interactions on the behavior of molecular torsion balances

the binding of rubromycin derivatives to telomerase and DNA polymerase

the reaction mechanism of copper-catalyzed addition of azides to iodoalkynes

I mostly work alone and therefore my papers, in the long run, will not be a profitable for them. I felt that I should give them some extra support in exchange for their extremely low number-of-authors-based APC.

As a mid-career researcher at a little-known teaching-based institution, I reasoned that this opportunity might increase my visibility and improve my CV.

I am enjoying my run as an editor. So far, I have shepherded seven papers through the publishing process: one of them was published a week ago, I rejected one "on arrival", and five of them are undergoing review. I target my peer-review invitations to people who have
recently published work using the same methods, or studied the same
question, both for the obvious expertise and hoping that they will find the paper interesting. Still, I was quite surprised with how hard it is to get people to accept reviewing papers: for two papers, I managed to get two reviewers with around 6-8 invitations, but my latest assignments required more than 15 invitations each! I understand that everybody is busy researching, writing papers, applying for funding, etc., but I never thought that the acceptance rate for peer-review requests would be < 15%. I do not get many peer-review request myself, but I do believe I have an obligation of accepting as many requests as possible (and reviewing them promptly), and I thought this was the "common" mindset... Maybe the people I target for my invitations are simply too senior and are therefore swamped with review requests, but the emails of "non-senior" members of a Lab are too often hard to find, due to the common practice of including only the the lab leader "corresponding author".

Wednesday, July 8, 2015

Each line in a $VEC group contains the coefficients of five basis
functions for a given orbital. These are formatted in a special way,
with seven numbers in each line. These numbers are:

1st) the
number of the orbital to which the coefficients belong (written with at
most two characters, so that 1 means orbital 1, .. , 99 means orbital
99, 00 means orbital 100) . This number is repeated in the beginning of
every line, until all coefficients for that orbital have been written

2nd)
this number tells the program how to assign the coefficients to the
basis functions. "1" means that the coefficients are for basis functions
1-5, "2" means that the coefficients are for basis functions 5-10, etc.
In general , that number "n" directs the program to assign the five
coefficients present in the line to basis functions 5*(n-1)+1 to 5*n.

3rd to 7th) coefficients of five basis functions

BETA orbitals are punched as a group immediately after all ALPHA orbitals.

This
format entails that in molecules with more than 100 orbitals the $VEC
group contains several blocks with the same 1st number. For example, in a
molecule with 200 orbitals, alpha orbital 27 is described by the first
block of lines beginning with "27", and alpha orbital 127 is described
by the SECOND block of lines beginning with "27".

I usually find
the beginning of the BETA orbitals by repeating a search for the string "
1 1" : if that string is preceded by a block beginning with "00 1", it
usually refers to orbitals 101, or 201, etc. (the exception being those
systems with exactly 100, 200, etc. orbitals). If string " 1 1" is NOT
preceded by a block beginning with "00 1", you are sure to have found
the beginnning of the BETA orbitals